Universidad Autónoma del Estado de méxico

facultad de química
farmacología Avanzada

nucleic acid inhibition

alumnos:
Juan Daniel Rojas Zuñiga
Justo Julian Diana Itzel
mechanism
Many antimicrobial agents can interfere at different levels
in the synthesis of nucleic acids:

● DNA replication
● preventing transcription
● inhibiting the synthesis of essential metabolites
 sulfonamides and trimethoprim
characterized by a benzene nucleus, an amino group (NH2) in
position 4, that is essential for its pharmacological
activity and a sulfomide group in position 1.
mechanism
These drugs competitively and sequentially block the
synthesis of bacterial folic acid, producing a
bacteriostatic effect.

folic acid intervenes in the synthesis of thymines, purines

and methionine, necessary for the synthesis of DNA and RNA
and proteins, necessary for bacterial growth
The structural analogous sulfas of p-aminobenzoic acid
(PABA) compete with the incorporation of this molecule
of folic acid, inhibiting the dihydropteroic synthetase
enzyme

trimethoprim contributes to the

inhibition of folic acid synthesis
(FH4), inhibits the
dihydrofolic-reductase enzyme,
blocks the passage of dihydrofolic
acid (FH2) and its necessary
cofactors for thymine synthesis
 microbial activity
sulfonamides:covers a wide variety of gram positive
microorganisms, fungi and protozoa

trimethoprim:small number of microorganisms

pharmacokinetics
orally: absorbed well in
the gastrointestinal tract

parenteral route: greater

absorption in the form of
salt and bind to proteins

are metabolized by
acetylation and
glucuronoconjugation and
are excreted by the kidney
therapeutic indications
sulfonamides are indicated in the following processes

● Chamydia infections
● urinary tractinfections
● dermatitis herpetiformis
● leprosy
● ulceratives colitis
qUINOLONES
Quinolones are derivatives toacid nalidíMexico. Fluorinated quinolones 4
asciprofloxacin and moxifloxacin They have broad antimicrobial activity and are
effective afterands of administrationorn oral for the treatment of a wide range of
infectious diseases.
The quinolones were a little-used drug class
until the early 1980s, when a second
qUINOLONES
generation of compounds was developed.
Displayed considerably improved activity
against gyrase, greater penetration into
Gram-positive organisms, and enhanced
pharmacokinetics and pharmacodynamics.
The most critical changes to the quinolone
skeleton were the introduction of a fluorine
at position C6 and a major ring substituent
(piperazine or methyl-piperazine) at C7
Because of the inclusion of the fluorine,
quinolones are often termed
“fluoroquinolones
MECHANISM OF ACTION
❏ The antibiotics derived from quinolone have a specific action on gyrase of bacterial DNA
and topoisomerase IV. For many gram-positive bacteria, topoisomerase IV is the main
target.
❏ In contrast, DNA gyrase represents the main target of quinolone in many gram-negative
organisms.
❏ Gyrase introduces negative superhelices in DNA to combat excessive positive superlices
that may occur during DNA replication.
❏ The quinolones inhibit gyrase-mediated DNA supercoiling and correlate well with the
needs to inhibit the development of bacteria (0.1 to 10 μg / ml). Mutations in the gene
encoding the A-gyrase subunit may confer resistance to these drugs.
 ANTIBACTERIAL SPECTRUM
❏ Fluoroquinolones are potent bactericidal microorganisms
against E. coli and various species of Salmonella,
Shigella, Enterobacter, Campylobacter and Neisseria.
❏ Fluoroquinolones also have a satisfactory activity against
staphylococci, but not againstmethicillin-resistant strains
❏ The activity against streptococci is limited to a subset of
the quinolones, such as levofloxacin, gatifloxacin and
moxifloxacin. Various intracellular bacteria are inhibited by
fluoroquinolones in concentrations that can be reached in
the plasma; these are species of Chlamydia,
Mycoplasma, Legionella, Brucella and Mycobacterium
(including Mycobacterium tuberculosis).
Absorption, distribution, metabolism and excretion.
The quinolones are well absorbed after oral administration.

Maximum serum concentrations of fluoroquinolones are

obtained within 1 to 3 hours of a oral dose of 400 mg.

The volume of distribution of the quinolones is considerable

and the concentrations in urine.

Food may delay the time to get the concentrations maximum

serum
The bioavailability of fluoroquinolones is greater than 50% for all compounds and
greater than 95% for others.

Quinolone concentrations in cerebrospinal fluid, bone tissue and prostatic fluid are
lower than in serum.

Most of the quinolones are eliminated predominantly in the kidney and the doses
must be adjusted in case of renal failure.

None of the drugs is efficiently eliminated by peritoneal dialysis or hemodialysis.

Pharmacokinetic aspects
fluoroquinolones are
compounds that depend
on the concentration
and duration, until
bacterial eradication
is achieved when the
ratios of the free
drug of the area under
the curve.
THERAPEUTIC USES
❏ Infections of the urinary tract bone, joint and soft tissue
infections of other infections.
Side Effects
In general, quinolones and fluoroquinolones are well
tolerated. Secondary reactions
They affect the digestive tract and 3 to 17% of patients report
mild nausea, vomiting and abdominal discomfort.
leprosy
It is a chronic infectious
disease caused by
Mycobacterium leprae,
which mainly affects skin
and peripheral nerves, can
affect other organs and
sometimes it is systemic.
 symptom
Unique dermatological lesions or multiple as:

Hypopigmented

Neurological injuries such as:

Thickening of peripheral nerve trunks, alterations of the sensitivity, motor

alterations (loss of strength or paralysis).
treatment
side effects

Kidney damage

hepatopathy

severe anorexia
 Rifampicina
Semisynthetic derivative of rifamycin, a complex macrocyclic
antibiotic that inhibits the synthesis of ribonucleic acid
in a wide range of pathogenic microbes.
mechanism of action
it binds to the beta
subunit of the
RNA-dependent DNA
polymerase.

preventing this enzyme

from binding to DNA,
blocking RNA transcription
gracias
 referencias
● http://www.cenaprece.salud.gob.mx/programas/interior/micobacteriosis/descargas/pdf/lepra.pdf
● velasquez: farmacologia basica y clinica, 17°ed., panamericana
● goodman and gilman: las bases de la farmacologia de la terapeutic, Mc Graw Hill, 10°edicion 2001